This project is concerned with establishing the best technique for transplantation of pancreatic islets tissue in diabetic animals, investigating methods of preservation of islet tissue, and circumventing the immunological response to transplanted allogenic islets. During the past year we have found that neonatal rat pancreatic islets remain viable and can be successfully transplanted after three hours of in situ donor warm ischemia. In addition, freshly recovered neonatal rat pancreatic islets can be preserved for up to 63 hours in tissue culture media at 4 degrees C and still ameliorate diabetes following transplantation. We have also found that adult rat pancreatic tissue can be dispersed and transplanted without specific islet isolation if exocrine atrophy is induced by prior treatment of the donors with DL-ethionine. A comparison of portal versus systemic venous transplantation of islet tissue in rats showed both to be successful, but that the portal site offered advantages beyond just providing an immediately blood supply. Using the totally pancreatectomized dog as an experimental model of diabetes, we have shown that 20 minutes of collagenase digestion is the optimal time prepared dispersed pancreatic tissue for autotransplantation to the spleen. This treatment results in normoglycemia. We found that the portal vein is not a good site for transplantation in the dog because of the development of portal hypertension. Dog pancreatic tissue can be preserved for up to 24 hours at 4 degrees C in tissue culture medium, but the frequency of success after transplantation is less than in rats. Allogenic pancreatic tissue transplanted to the spleen of totally pancreatectomized immunosuppressed dogs was rapidly rejected in two-thirds of canine recipients, but in one-third of the dogs the tissue was accepted for a prolonged periods. We have also developed a mouse model of islet transplantation using neonatal donors this past year. In the coming year we plan to use a mouse model of diabetes and transplantation for allograft experiments. Islet allograft experiments in rats will also be done using various donor pretreatment regimens. The use of donors pretreated with DL-ethionine will be extended to dogs, and will also be used as an adjuvant to culture of pancreati (Text Truncated - Exceeds Capacity)